Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction  

作　　者：Zhenyu Zhao Huitong Ruan Aopan Chen Wei Xiong Mingzhu Zhang Ming Cai Wenguo Cui 

机构地区：[1]Department of Orthopaedics,Shanghai Tenth People's Hospital,School of Medicine,Tongji University No.301 Middle Yanchang Road,Shanghai 200072,China [2]Department of Orthopaedics,Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases,Shanghai Institute of Traumatology and Orthopaedics,Ruijin Hospital,Shanghai Jiao Tong University Schoolof Medicine,197 Rujin 2nd Road,Shanghai 200025,China [3]Department of Foot and Ankle Surgery,Beijing Tongren Hospital,Capital Medical University,1 Dongjiao Minxiang,Beijing 100730,China

出　　处：《Research》2024年第2期431-447,共17页研究（英文）

基　　金：supported by the National Key Research and Development Program of China(2020YFA0908200);the National Natural Science Foundation of China(82272176 and 82003658);the Shanghai Science and Technology Commission(19411963100);the Shanghai Municipal Health and Family Planning Commission(2022XD055);the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906).

摘　　要：Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.

关 键 词：SUSTAINED RELEASE LINKING 

分 类 号：TQ427.26[化学工程]